Pseudomonas aeruginosa has long been known to produce phenotypic variants during chronic mucosal surface infections. These variants are thought to be generated to ensure bacterial survival against the diverse challenges in the mucosal environment. Studies have begun to elucidate the mechanisms by which these variants emerge in vitro; however, too little information exists on phenotypic variation in vivo to draw any links between variants generated in vitro and in vivo. Consequently, in this study, the P. aeruginosa gacS gene, which has previously been linked to the generation of small colony variants (SCVs) in vitro, was studied in an in vivo mucosal surface infection model. More specifically, the rat prostate served as a model mucosal surface to test for the appearance of SCVs in vivo following infections with P. aeruginosa gacS− strains. As in in vitro studies, deletion of the gacS gene led to SCV production in vivo. The appearance of these in vivo SCVs was important for the sustainability of a chronic infection. In the subset of rats in which P. aeruginosa gacS− did not convert to SCVs, clearance of the bacteria took place and healing of the tissue ensued. When comparing the SCVs that arose at the mucosal surface (MS-SCVs) with in vitro SCVs (IV-SCVs) from the same gacS− parent, some differences between the phenotypic variants were observed. Whereas both MS-SCVs and IV-SCVs formed dense biofilms, MS-SCVs exhibited a less diverse resistance profile to antimicrobial agents than IV-SCVs. Additionally, MS-SCVs were better suited to initiate an infection in the rat model than IV-SCVs. Together, these observations suggest that phenotypic variation in vivo can be important for maintenance of infection, and that in vivo variants may differ from in vitro variants generated from the same genetic parent.

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Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor.

Amiodarone is an antiarrhythmic medication with many side effects. Neuromyopathy is a rare adverse effect. We present an 87-year-old woman with bilateral leg pain and weakness in the context of amiodarone. She was admitted to the Acute Geriatric Unit in Calgary, Alberta, Canada. On examination, hip flexor and extensor strength were 2/5 bilaterally while knee flexor and extensor strength were 4/5 and 3/5, respectively. Creatine kinase and C-reactive protein levels were normal. MRI of the lumbar spine showed mild central canal stenosis. Electromyography and nerve conduction testing showed a severe axonal length-dependent polyneuropathy of the left lower extremity. There was evidence of myopathic changes to the left iliopsoas muscle. Overall, a neuromyopathic process affecting the lower extremities was supported. After discontinuation of amiodarone, mobility and function significantly improved. Although a rare complication of amiodarone, neuromyopathy should be considered in patients with compatible symptomatology.

OBJECTIVE To investigate the effect of iohexol on standardized quantitative urine culture results in dogs. The authors hypothesized that the presence of iohexol in inoculated urine samples would result in lower bacterial concentrations (CFU/mL) and, therefore, decrease culture sensitivity. SAMPLE Urine samples were aseptically collected during cystoscopy from a single client-owned dog untreated with antimicrobials. PROCEDURES An experimental controlled study. The urine sample was divided into 38 aliquots (0.5 mL each) that were used as negative controls or inoculated with an equal amount of Escherichia coli (105 CFU/mL). Different volumes (0.1 and 0.5 mL) of contrast or saline were added to the aliquots and quantitative culture results were compared. Two different incubation times between the preparation of aliquots and culture were evaluated (15 minutes and 24 hours). RESULTS All aliquots from samples inoculated with E. coli (positive controls and iohexol-group) had the same reported quantitative result (104 CFU/mL). No growth was reported for the negative controls. Iohexol did not show any anti-E. coli properties in canine urine cultures for dilutions up to 1:2 contrast:urine and concentrations up to 120 mgI/mL. No difference was reported when iohexol was incubated with inoculated urine for 15 minutes or 24 hours. CLINICAL RELEVANCE Based on the experimental in vitro conditions described, administration of iohexol before the collection of urine during urologic procedures does not negatively impact the isolation and growth of E. coli.